We are developing biosensor arrays that are based on microfabricated silicon flexural plate wave (FPW) resonators coated with molecular recognition chemistry. The resonators within the micro-chemical ...analysis array (μCANARY) are micro-electromechanical (MEM) sensors that have been miniaturized to allow many independently addressable sensors to be integrated within a single silicon chip. The target analyte of an individual sensor within the chip is selectively detected by depositing molecular recognition component (or “coating”) onto the sensor surface, and monitoring changes in the frequency and phase of the resonance as the coating interacts with the analyte. The ultimate goal of this project is integration of hundreds of miniature resonators within a single chip for detection of biological species. As proof of concept demonstration, we describe here the detection of proteins and intact microorganisms using 2-element and 8-element μCANARY sensor chips and address electronics. Preliminary results of sensitivity, selectivity, and surface regeneration methods of the sensor are presented. Detection of proteins and microorganisms with the μCANARY sensor were confirmed by optical measurements.
Percutaneous left atrial appendage occlusion aims to reduce the risk of stroke in patients with AF, particularly those who are not good candidates for systemic anticoagulation. The procedure has been ...studied in large international randomised trials and registries and was approved by the National Institute for Health and Care Excellence in 2014 and by NHS England in 2018. This position statement summarises the evidence for left atrial appendage occlusion and presents the current indications. The options and consensus on best practice for pre-procedure planning, undertaking a safe and effective implant and appropriate post-procedure management and follow-up are described. Standards regarding procedure volume for implant centres and physicians, the role of multidisciplinary teams and audits are highlighted.
A chemical vapor detection and biosensor array based on microfabricated silicon resonators coated with thin film polymer sorption layers is described. The resonators within the array are ...micro-electromechanical (MEM) flexural plate wave (FPW) sensors that have been miniaturized to allow many independently addressable sensors to be integrated within a single silicon chip. The target analyte of an individual sensor within the chip is selected by placing a polymer coating onto the resonating membrane. Detection is performed by monitoring changes in the frequency and damping factor of the resonance as the coating interacts with the environment. This work documents vapor response characterization of an individual sensor element within an array and reports on the operation of an eight-element sensor array. Polymer coatings targeted toward detection of chemical weapon agents have been applied to the sensor and chemical vapor exposure tests using two chemical weapon simulants and four vapor phase interferents have been performed. Data describing temperature dependence, long-term/short-term drift stability, detection limits, detection linearity and vapor selectivity will be presented. The use of resonant damping information is shown to provide the ability to discriminate between vapor analytes that produce equal resonant frequency shifts.
This study was designed to test the hypothesis that significant maternal physiologic adaptations to pregnancy take place in multiple systems long before they are functionally necessary (during the ...embryonic period). To test this hypothesis, 20 women were studied serially before pregnancy and in the seventh and fifteenth postconceptional week of an accurately dated, clinically normal, singleton pregnancy. By the seventh week, significant changes were noted in body composition and cardiopulmonary and metabolic functions. Body fat and plasma volume increased 2% and 11%, respectively, accounting for all of the observed 2 kg weight gain. With the patient standing at rest after eating, heart rate increased 13 beats/min (16%) while mean arterial pressure fell 8 mm Hg (9%). Minute ventilation rose 24% and oxygen consumption increased by 27 ml/min, or 10%. The postprandial respiratory exchange ratio also increased, from 0.78 to 0.83; the whole blood glucose level was unchanged at rest, although there was a 15% decrease in whole blood lactate levels. We conclude that our hypothesis is correct, which suggests these adaptations are preparative and may have diagnostic value.
We examined the reliability of self-reported alcohol consumption in past age periods of women's lives. As part of a case-control study of breast cancer conducted in Massachusetts and Wisconsin in ...1988-1991, the same questionnaire was administered for a second time to 211 controls (mean age = 54 years) after an interval of 6-12 months. The Spearman correlation coefficients between the average number of grams of alcohol consumed daily reported in the two interviews, by age period of consumption, were: 16-19 years, r = 0.81; 20-29 years, r = 0.84; 30-39 years, r = 0.75; and for recent consumption, r = 0.77. Self-reported alcohol consumption throughout adult life was reported with precision sufficient to make the ranking of subjects' intake consistent between interviews.
Cells harvested from Fanconi anemia (FA) patients show an increased hypersensitivity to the multifunctional DNA damaging agent mitomycin C (MMC), which causes cross-links in DNA as well as ...7,8-dihydro-8-oxoguanine (8-oxoG) adducts indicative of escalated oxidative DNA damage. We show here that the Drosophila multifunctional S3 cDNA, which encodes an N-glycosylase/apurinic/apyrimidinic (AP) lyase activity was found to correct the FA Group A (FA(A)) and FA Group C (FA(C)) sensitivity to MMC and hydrogen peroxide (H2O2). Furthermore, the Drosophila S3 cDNA was shown to protect AP endonuclease deficient E. coli cells against H2O2 and MMC, and also protect 8-oxoG repair deficient mutM E. coli strains against MMC and H2O2 cell toxicity. Conversely, the human S3 protein failed to complement the AP endonuclease deficient E. coli strain, most likely because it lacks N-glycosylase activity for the repair of oxidatively-damaged DNA bases. Although the human S3 gene is clearly not the genetic alteration in FA cells, our results suggest that oxidative DNA damage is intimately involved in the overall FA phenotype, and the cytotoxic effect of selective DNA damaging agents in FA cells can be overcome by trans-complementation with specific DNA repair cDNAs. Based on these findings, we would predict other oxidative repair proteins, or oxidative scavengers, could serve as protective agents against the oxidative DNA damage that occurs in FA.
We investigated the survival and chimeric engraftment characteristics of a large consecutive series of lambs that were transplanted with human hematopoietic cells in utero. Approximately 50% of the ...fetal sheep survived. Neither the transplantation of human cells into fetal sheep, nor the parity of the ewe was associated with increased mortality, as compared with the risk of surgery alone. However, a breed-associated mortality was noted. Sixty percent of surviving recipient lambs contained donor, human hematopoietic cells in blood and bone marrow (BM) cells. Chimerism ranged from 0.0001-1%. Human hematopoietic progenitors were identified in the BM in 8 of 12 chimeric sheep examined. Some lambs engrafted with human cells maintained a human chimerism for up to at least 2 years. Our data demonstrate that a large proportion of fetal sheep are capable of engrafting human cells, albeit at widely variable levels of engraftment.
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